US00755.71 77B2

(12) United States Patent (10) Patent No.: US 7,557,177 B2 Fansler et al. (45) Date of Patent: Jul. 7, 2009

(54) RING-OPENED AZLACTONE INITIATORS 6,747,104 B1 6/2004 Wendland et al. FORATOM TRANSFER RADICAL 6,753,391 B1 6/2004 Lewandowski et al. POLYMERIZATION 6,762.257 B1 7/2004 Lewandowski et al. 6,784,264 B2 * 8/2004 Lewandowski et al...... 526.204 (75) Inventors: Duane D. Fansler, Dresser, WI (US); 6,784,265 B2 8/2004 Fansler et al. Kevin M. Lewandowski, Inver Grove 6,818,716 B2 11/2004 Wendland et al. Heights, MN (US); Babu N. Gaddam, 6,841,637 B2 1/2005 Lewandowski et al. Woodbury, MN (US); Steven M. 6,894,133 B2 5/2005 Lewandowski et al. Heilmann, Afton, MN (US); Larry R. 6,908,952 B2 6/2005 Lewandowski et al. Krepski, White Bear Lake, MN (US); 6,911,510 B2 6/2005 Lewandowski et al. Stephen B. Roscoe, Saint Paul, MN 6,969,749 B2 11/2005 Lewandowski et al. (US); Michael S. Wendland, North 6,992,217 B2 * 1/2006 Fansler et al...... 562 567 Saint Paul, MN (US) 7,041,755 B2 5/2006 Lewandowski et al. 2004/0116633 A1 6/2004 Fansler et al. (73) Assignee: 3M Innovative Properties Company, 2004/O152852 A1 8/2004 Lewandowski et al. St. Paul, MN (US) 2004/0152853 A1 8/2004 Fansler et al. 2004/O198933 A1 10, 2004 Wendland et al. (*) Notice: Subject to any disclaimer, the term of this 2004/0225.090 A1 11/2004 Lewandowski et al. patent is extended or adjusted under 35 2004/0225,091 A1 11/2004 Lewandowski et al. U.S.C. 154(b) by 4 days. 2005/0065300 A1 3/2005 Lewandowski et al. 2005/0192370 A1* 9, 2005 Fansler et al...... 522f1 (21) Appl. No.: 11/868,793 2006/0074211 A1* 4/2006 Fansler et al...... 526,319 2006/O128825 A1 6/2006 Fansler et al...... 522,115 (22) Filed: Oct. 8, 2007 2006/0165999 A1* 7/2006 Fansler et al...... 428/411.1 (65) Prior Publication Data 2007/019 1564 A1* 8, 2007 Fansler et al...... 526,319 US 2008/OO27210 A1 Jan. 31, 2008 FOREIGN PATENT DOCUMENTS Related U.S. Application Data WO WO 96/30421 10, 1996 (62) Division of application No. 11/081,218, filed on Mar. WO WO97, 18247 5, 1997 16, 2005, now Pat. No. 7,294,742, which is a division WO WO99,31144 6, 1999 of application No. 10/316,334, filed on Dec. 11, 2002, WO WOO2,24761 A1 3, 2002 now Pat. No. 6,992,217. WO WOO2,26836 A2 4, 2002 WO WOO2,28914 A2 4/2002 (51) Int. Cl. WO WO 2004/052943 A1 6, 2004 C08G 69/26 (2006.01) WO WO 2004/052944 A1 6, 2004 (52) U.S. Cl...... 528/332: 528/367:528/369; WO WO 2004/072127 A1 8, 2004 525/308: 525/314: 556/31556/110:556/136; WO WO 2004/072139 A1 8, 2004 556/138: 562/567; 562/574; 526/135; 526/146; 526/147; 526/204; 526/220; 526/307.1; 526/317.1: 526/318; 526/319; 560/70 (Continued) (58) Field of Classification Search ...... 528/332, 528/367, 369; 525/308,314: 556/31, 110, OTHER PUBLICATIONS 556/136, 138: 562/567,574; 526/135, 146, A. Sebenik “Living Free-Radical Block Copolymerization Using 526/147, 204, 220, 307.1, 317.1, 318, 319; Thio-Iniferters”. Prog. Polym. Sci., (1998), pp. 875-917, vol. 23. 560/70 “Polyazlactones'. Encyclopedia of Polymer Science and Engineer See application file for complete search history. ing, (1988), pp. 558-570, vol. 11, 2" Edition, John Wiley and Sons. K. Matyjaszewski et al., “Atom Transfer Radical Polymerization'. (56) References Cited Chemical Reviews, (2001), pp. 2921-2990, vol. 101, No. 9. U.S. PATENT DOCUMENTS (Continued) 4,304,705 A 12, 1981 Heilmann et al. 5,097,007 A 3, 1992 Himori Primary Examiner Ling-Siu Choi 5,314,962 A 5, 1994 Otsu et al. Assistant Examiner—Bijan Ahvazi 5,356,947 A 10, 1994 Ali et al. (74) Attorney, Agent, or Firm Kent S. Kokko 5,506,279 A * 4, 1996 Babu et al...... 522/34 5,527,921 A * 6/1996 Haubrich ...... 548,334.5 (57) ABSTRACT 5,763,548 A 6/1998 Matyjaszewski et al. 6,143,848 A 11/2000 Lee et al. 6,310,149 B1 10/2001 Haddleton Initiators for atom transfer radical polymerizations are 6,407,187 B1 6/2002 Matyjaszewski et al. described. The initiators have an azlactone or ring-opened 6,448,337 B1 * 9/2002 Gaddam et al...... 525, 193 aZlactone moiety to provide telechelic (co)polymers. 6,677,413 B1 1/2004 Lewandowski et al. 6,680,362 B1 1/2004 Fansler et al. 13 Claims, No Drawings US 7,557,177 B2 Page 2

FOREIGN PATENT DOCUMENTS Polymerization: The RAFT Process'. Macromolecules, (1999), pp. 2071-2074, vol. 32, American Chemical Society. WO WO 2004/094484 A1 11, 2004 WO WO 2004/0944.85 A1 11, 2004 M. Freemantle, “In Control of a Living Process”. Chemical and WO WO 2004/099275 A1 11, 2004 Engineering News, (Sep. 9, 2002), pp. 36-40. WO WO 2004/099276 A1 11, 2004 G. B. Fields et al., “Solid Phase Peptide Synthesis Utilizing 9-fluorenylmethoxycarbonyl Amino Acids”. International Journal of OTHER PUBLICATIONS Peptide & Protein Research, (1990), pp. 161-214, vol. 35. J.S. Wang, “Controlled “Living” Radical Polymerization, Halogen G. B. Fields et al., Chapter 3, “Principles and Practice of Solid-Phase Atom Transfer Radical Polymerization Promoted by a Cu(I)/Cu(II) Peptide Synthesis”. Synthetic Peptides: A User's Guide, G. A. Grant Redox Process', Macromolecules, (Nov. 6, 1995), pp. 7901-7910, Edition, (1992), pp. 77-183, W. H. Freeman and Co., New York, NY. vol. 28, No. 23. W. B. Lawson et al., “Modification of a Methionine Residue Near the S. M. Heilmann, "Chemistry and Technology of 2-Alkenyl Active Site of Chymotrypsin'. J. Am. Chem. Soc., (1962), pp. 2017 Azlactones”,Journal of Polymer Science: Part A: Polymer Chemis 2018, vol. 84. try, (2001), pp. 3655-3677, vol.39, John Wiley and Sons, Inc. Registry No. 151142-96-0, ACS on STN. (2005), p. 1. Y. K. (Bill) Chong, "A More Versatile Route to Block Copolymers and Other Polymers of Complex Architecture by Living Radical * cited by examiner US 7,557,177 B2 1. 2 RING-OPENED AZLACTONE NITIATORS trolled radical polymerization process which provides telech FORATOM TRANSFER RADICAL elic (co)polymers capable of entering into further POLYMERIZATION polymerization or functionalization through reactive end groups, particularly electrophilic end groups. This application is a divisional of U.S. Ser. No. 11/081,218, filed Mar. 16, 2005, now U.S. Pat. No. 7,294,742; which is a SUMMARY OF THE INVENTION divisional of U.S. Ser. No. 10/316,334, filed Dec. 11, 2002, now U.S. Pat. No. 6,992,217, the disclosures of which are The present invention provides initiators for atom transfer herein incorporated by reference. radical polymerization processes that comprise compounds 10 of the formula: FIELD OF THE INVENTION The present invention provides initiators and initiator sys tems for atom transfer radical polymerization (ATRP) pro CCSSCS. 15 BACKGROUND In conventional radical polymerization processes, the polymerization terminates when reactive intermediates are destroyed or rendered inactive; radical generation is essen tially irreversible. It is difficult to control the molecular wherein X is Cl, Br, or a pseudohalogen group; weight and the polydispersity (molecular weight distribution) RandR are eachindependently selected from X, H, an alkyl of polymers produced by conventional radical polymeriza group, a cycloalkyl group, a heterocyclic group, an arenyl tion, and difficult to achieve a highly uniform and well-de 25 group and an aryl group, or R' and R taken together with fined product. It is also often difficult to control radical poly the carbon to which they are attached form a carbocyclic merization processes with the degree of certainty necessary in ring: specialized applications, such as in the preparation of end R and R are each independently selected from an alkyl functional polymers, block copolymers, star (co)polymers, group, a cycloalkyl group, an aryl group, an arenyl group, and other novel topologies. 30 In a controlled radical polymerization process radicals are or RandR' taken together with the carbon to which they generated reversibly, and irreversible chain transfer and chain are attached form a carbocyclic ring; termination are absent. There are four major controlled radi Q is a linking group selected from a covalent bond, cal polymerization methodologies: atom transfer radical (—CH2—), CO-O-(CH2) , CO. O. polymerization (ATRP), reversible addition-fragmentation 35 (CHCHO). , —CO NR (CH) , —CO S chain transfer (RAFT), nitroxide-mediated polymerization (CH2). , where o is 1 to 12, and R is H, an alkyl group, (NMP) and iniferters, each method having advantages and a cycloalkyl group or an aryl group; and disadvantages. n is 0 or 1. Atom transfer radical polymerization (ATRP) has been The present invention also provides initiators that comprise described as a simple, versatile and efficient controlled radi 40 the ring-opened reaction product of the initiators of Formula cal polymerization process. See M. Freemantle, “In Control I and a reactive compound, Such as an aliphatic compound, of a Living Process”, Chemical and Engineering News, Sep. having one or more nucleophilic groups. Such initiators have 9, 2002, pp. 36-40, ATRP processes typically employ an alkyl the general formula: halide as an initiator and a transition metal complex as a 45 catalyst to produce a polymeric radical in the presence of a II OOC. R1 O R3 O Atom transfer radical polymerization systems based on the combination of a transition metal halide and an alkyl halide (CH2) --z --Rs have been described. “Atom transfer” refers to the transfer of x--o-I-Nil R2 the halogen atom between the transition metal and the poly 50 mer chain. For example, K. Matyjaszewski, (Macronol ecules, vol. 28, 1995, pp. 7901-7910 and WO 96/30421) describes the use of CuX (where X—Cl, Br) in conjunction wherein with bipyridine and an alkyl halide to give polymers of nar X is Cl, Br, or a pseudohalogen group; row molecular weight distribution and controlled molecular 55 R" and Rare each independently selected from X, H, an weight. A comprehensive review of ATRP is provided by alkyl group, a cycloalkyl group, an arenyl group, a het Matyjaszewski and Xia, Chem. Rev., vol. 101, pp. 2921-2990, erocyclic group and an aryl group or R' and R taken 2001. together with the carbon to which they are attached form Thus, there is a need for a radical polymerization process a carbocyclic ring; which provides (co)polymers having a predictable molecular 60 R and R are each independently selected from an alkyl weight and a narrow molecular weight distribution (low group, a cycloalkyl group, an aryl, an arenyl group, or R "polydispersity'). A further need is strongly felt for a radical and R' taken together with the carbon to which they are polymerization process which is sufficiently flexible to pro attached form a carbocyclic ring; vide a wide variety of products, but which can be controlled to n is 0 or 1; the degree necessary to provide highly uniform products with 65 Z is O, S or NR", wherein R is H, an alkyl group, a a controlled structure (i.e., controllable topology, composi cycloalkyl group, an arenyl group, a heterocyclic group tion, Stereoregularity, etc.). There is further need for a con or an aryl group: US 7,557,177 B2 3 4 R is an organic or inorganic moiety and has a valency ofm. The term "heterocyclic group' or "heterocycle” means the R is the residue of a mono- or polyfunctional compound monovalent residue remaining after removal of one hydrogen of the formula R(ZH): atom from an cycloaliphatic or aromatic compound having Q is a linking group selected from a covalent bond, one ring or two fused rings having 5 to 12 ring atoms and 1 to (—CH2—), CO-O-(CH2) , CO. O. 3 heteroatoms selected from S, N, and nonperoxidic O. Use (CH2CH2O), . CO. NR (CH) , CO ful heterocycles include azlactone, pyrrole, furan, thiophene, S—(CH) , where o is 1 to 12, and R is H, an alkyl imidazole, pyrazole, thiazole, oxazole, , piperazine, group, a cycloalkyl group, an arenyl group, a heterocy piperidine, hydrogenated and partially hydrogenated deriva clic group or an aryl group: tives thereof m is an integer of at least 1, preferably at least 2. 10 The term “multifunctional' means the presence of more In another aspect, the present invention provides an initia than one of the same functional reactive group; tor system for controlled radical polymerization comprising The term “multireactive” means the presence of two or the above-described initiators and a transition metal com more of two different functional reactive groups; pound that participates in a reversible redox cycle. The term “polyfunctional' is inclusive of multireactive and The initiators, and initiator systems of the present invention 15 multifunctional. provide (co)polymers having a predictable molecular weight The term “acid catalyst” or “acid catalyzed' means cataly and a narrow molecular weight distribution. Advantageously, sis by a Bronsted- or Lewis-acid species: the initiators provide novel multireactive addition polymers The term “molecular weight' means number average having first and second terminal reactive groups that may be molecular weight (M), unless otherwise specified. used for further functionalization. The present invention fur The term “pseudohalogen refers to polyatomic anions that ther provides a controlled radical polymerization process use resemble halide ions in both their acid-base and redox chem ful in the preparation of terminal-functionalized (telechelic) istry and have relatively low basicity generally, and form a (co)polymers, block copolymers, star (co)polymers, graft free radical under ATRP conditions. Useful psuedohalogens copolymers, and comb copolymers. The process provides include, for example, cyanide, cyanate, thiocyanate, thiosul these (co)polymers with controlled topologies and composi 25 tions. fate, Sulfonylhalides and azide ions. The control over molecular weight and functionality The term (co)polymer refers to homo- and copolymers. obtained in this invention allows one to synthesize numerous The term (meth)acrylate refers to both methacrylate and materials with many novel topologies for applications in coat acrylate. ings, Surface modifications, elastomers, Sealants, lubricants, 30 pigments, personal care compositions, composites, inks, DETAILED DESCRIPTION adhesives, water treatment materials, hydrogels, imaging materials, telechelic materials and the like. The present invention provides novel initiators of Formula In another aspect, the invention provides a method for I and the corresponding ring-opened initiators of Formula II polymerization of one or more olefinically unsaturated mono 35 for controlled radical polymerization processes. mers comprising addition polymerizing one or more olefini cally unsaturated monomers using the initiator system com prising the azlactone initiators, or the ring-opened azlactone R3 initiator and a transition metal compound that participates in X N R4 a reversible redox cycle. 40 and It is to be understood that the recitation of numerical ranges R R2 () by endpoints includes all numbers and fractions Subsumed within that range (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, ". O 4, and 5). II It is to be understood that all numbers and fractions thereof 45 are presumed to be modified by the term “about.” R1 O R3 O It is to be understood that “a” as used herein includes both the singular and plural. x-Ho-I-Nil cis-I-z-R The general definitions used herein have the following R2 R4 meanings within the scope of the present invention. 50 The term “alkyl refers to straight or branched, cyclic or acyclic hydrocarbon radicals, such as methyl, ethyl, propyl. wherein butyl, octyl, isopropyl, tert-butyl, sec-pentyl, cyclohexyl, and X is Cl, Br, or a pseudohalogen group, the like. Alkyl groups include, for example, 1 to 18 carbon RandR are eachindependently selected from X, H, an alkyl atoms, preferably 1 to 12 carbon atoms, or most preferably 1 55 group of 1 to 18 carbonatoms, a cycloalkyl group having 3 to 6 carbon atoms. to 14 carbonatoms, an aryl group having 6 to 12 ring atoms, The term “aryl' means the monovalent residue remaining an arenyl group having 6 to 26 carbonatoms, a heterocyclic after removal of one hydrogen atom from an aromatic com group having one ring or two fused rings having 5 to 12 ring pound which can consist of one ring or two fused or catenated atoms and 1 to 3 heteroatoms selected from S, N, and rings having 6 to 12 carbon atoms. 60 nonperoxidic O; or R' and R taken together with the car The term “arenyl' means the monovalent residue remain bon to which they are attached form a carbocyclic ring ing after removal of a hydrogenatom from the alkylportion of containing 4 to 12 ring atoms. a hydrocarbon containing both alkyl and aryl groups having 6 R and R are each independently selected from an alkyl to 26 atoms. group having 1 to 18 carbon atoms, a cycloalkyl group The term “azlactone' means 2-oxazolin-5-one groups and 65 having 3 to 14 carbon atoms, an aryl group having 5 to 12 2-oxazolin-6-one groups of Formula I, where n is 0 and 1. ring atoms, an arenyl group having 6 to 26 carbon atoms respectively. and 0 to 3 S, N, and nonperoxidic Oheteroatoms, or Rand US 7,557,177 B2 5 6 R' taken together with the carbon to which they are Such as ammonia, , trimethylamine, trimethylphos attached form a carbocyclic ring containing 4 to 12 ring phine, tributylphosphine, triphenylamine, triphenylphos atoms; phine, triphenylarsine, tributylphosphite; nitriles Such as Z is O, NH, S or NR", wherein R is a H, an alkyl group, an acetonitrile, benzonitrile; isonitriles Such as phenylisonitrile, aryl group and arenyl group or a heterocyclic group; 5 butylisonitrile; carbenegroups such as ethoxymethylcarbene, R is an organic or inorganic moiety and has a valency of m; dithiomethoxycarbene; alkylidenes Such as methylidene and m is an integer of at least 1, preferably 1 to 8, most preferably ethylidene. at least 2; Suitable polydentate compounds or groups include dipy Q is a linking group selected from a covalent bond, ridyl, 1.2-bis(diphenylphosphino)ethane, 1.2-bis(dipheny (—CH2—), CO-O-(CH2) , CO. O. 10 larsino)ethane, bis(diphenylphosphino)methane, polyamines (CH2CH2O). , —CO NR (CH) , —CO S Such as ethylenediamine, propylenediamine, tetramethyl eth (CH2). , where o is 1 to 12, and R is H, an alkyl group, ylene diamine, hexamethyl tris-aminoethylamine, diethylen a cycloalkyl group or an aryl group; etriamine, 1,3-diisocyanopropane, and hydridotripyra and n is 0 or 1. Zolylborate; the hydroxycarboxylic acids such as glycolic The present invention also provides initiator systems for 15 acid, lactic acid, salicylic acid; polyhydric phenols such as controlled radical polymerization comprising the initiators of catecholand 2,2'-dihydroxybiphenyl; hydroxyamines such as Formulas I and/or II and a transition metal compound that ethanolamine, propanolamine, and 2-aminophenol; dithio participates in a reversible redox cycle, e.g. Cu' ('Cu'. Use carbamates such as diethyldithiocarbamate, dibenzyldithio ful transition metal compounds have the general formula carbamate:Xanthates Such as ethylxanthate, phenylxanthate: |MLI"A, wherein M is a transition metal, generally in a the dithiolenes such as bis(perfluoromethyl)-1,2-dithiolene; low valency state, L is a , A- is an anion, n is the aminocarboxylic acids Such as alanine, glycine and o-ami formal charge on the transition metal having a whole num nobenzoic acid; dicarboxylic diamines as oxalamide, biuret; ber value of 1 to 7, preferably 1 to 3, and p is the number of diketones such as 2.4-pentanedione; hydroxyketones such as on the transition metal having an number value of 2-hydroxyacetophenone; alpha-hydroxyoximes Such as Sali 1 to 9, preferably 1 to 2. 25 cylaldoxime; ketoximes such as benzil oXime; 1,10-phenan Useful transition metals, M'", include the low valent states throline, porphyrin, cryptands and crown ethers, such as of Cu, Fe, Ru, Cr, Mo, Pd, Ni, Pt, Mn, Rh, Re, Co, V, Zn, Au, 18-crown-6 and glyoximes Such as dimethylglyoxime. Nb and Ag. Preferred low valent metals include Cu(I), Fe(II), Other suitable ligands that can coordinate to the transition Co(II), Ru(II) and Ni(II). Other valent states of these same metal through a O-bond are the inorganic groups such as, for metals may be used, and the active low Valent state generated 30 example, F, OH, Cl, Br, I, and Hand the organic groups in situ. such as, for example, CN, SCN, acetoxy, formyloxy, ben Useful anions, A, include halogen, C-C-alkoxy, NO, Zoyloxy, and the like. The ligand can also be a unit of a SO, PO, HPO, PF, triflate, hexafluorophosphate, polymer; for example the amino group in poly(ethyleneam methanesulfonate, arylsulfonate, CN and alkyl carboxylates ine); the phosphino group in poly(4-vinylphenyldiphe and aryl carboxylates. 35 nylphosphine); the carboxylic acid group in poly(acrylic The ligand, L, is used to Solubilize the transition metal salts acid); and the isonitrile group in poly(4-vinylphenylisoni in a suitable solvent and adjust the redox potential of the trile). transition metal for appropriate reactivity and selectivity. The Useful ligands containing two or more carbonatoms which ligands can direct the metal complex to undergo the desired can coordinate to the transition metal through a U-bond are one-electronatom transfer process, rather than a two-electron 40 provided by any monomeric or polymeric compound having process such as oxidative addition/reductive elimination. The an accessible unsaturated group, i.e., an ethylenic, —C=C- ligands may further enhance the stability of the complexes in group; acetylenic. —C=C- group; or aromatic group the presence of different monomers, solvents or at different which has accessible L-electrons regardless of the total temperatures. Acidic monomers and monomers that strongly molecular weight of the compound. complex transition metals may still be efficiently polymer 45 Illustrative of U-bond ligands are the linear and cyclic ized by appropriate selection of ligands. ethylenic and acetylenic compounds having less than 100 Useful ligands include those having one or more nitrogen, carbonatoms (when monomeric), preferably having less than oxygen, phosphorus and/or Sulfur atoms which can coordi 60 carbon atoms, and from Zero to 10 hetero atoms selected nate to the transition metal through a O-bond, ligands con from nitrogen, Sulfur, non-peroxidic oxygen, phosphorous, taining two or more carbonatoms which can coordinate to the 50 arsenic, selenium, boron, aluminum, antimony, tellurium, transition metal through a U-bond, and ligands which can silicon, germanium, and tin, the ligands being those such as coordinate to the transition metal through a u-bond or an ethylene, acetylene, propylene, methylacetylene, C.-butene, m-bond. 2-butene, diacetylene, butadiene, 1,2-dimethylacetylene, Useful ligands include those having one or more nitrogen, cyclobutene, pentene, cyclopentene, hexene, cyclohexene, oxygen, phosphorus and/or Sulfur atoms which can coordi 55 1.3-cyclohexadiene, cyclopentadiene, 1,4-cyclohexadiene, nate to the transition metal through a O-bond are provided by cycloheptene, 1-octene, 4-octene, 3,4-dimethyl-3-hexene, monodentate and polydentate compounds preferably con and 1-decene, m-allyl, m-pentenyl, norbomadiene, m-cy taining up to about 30 carbonatoms and up to 10 hetero atoms clohexadienyl, cycloheptatriene, cyclooctatetraene, and Sub selected from aluminum, boron, nitrogen, Sulfur, non-peroX stituted and unsubstituted carbocyclic and heterocyclic aro idic oxygen, phosphorus, arsenic, selenium, antimony, and 60 matic ligands having up to 25 rings and up to 100 carbon tellurium, where upon addition to the metal atom, following atoms and up to 10 hetero atoms selected from nitrogen, loss of Zero, one, or two hydrogens, the polydentate com Sulfur, non-peroxidic oxygen, phosphorus, arsenic, selenium, pounds preferably forming with the metal, M', a 4-, 5-, or boron, aluminum, antimony, tellurium, silicon, germanium, 6-membered Saturated or unsaturated ring. Examples of Suit and tin, such as, for example, m-cyclopentadienyl, , able monodentate compounds or groups are carbon monox 65 mesitylene, toluene, Xylene, tetramethylbenzene, hexameth ide, alcohols such as ethanol, butanol, and phenol; pyridine, ylbenzene, fluorene, naphthalene, anthracene, chrysene, nitrosonium (i.e., NO"); compounds of Group Vb elements pyrene, m-cycloheptatrienyl, triphenylmethane, paracyclo US 7,557,177 B2 7 8 phane, 1,4-diphenylbutane, m-pyrrole, m-thiophene, m-fu diimides, or preferably by treatment with ethyl chloroformate ran, pyridine, gamma-picoline, quinaldine, benzopyrane, and a trialkylamine, which proceeds through a mixed car thiochrome, benzoxazine, indole, acridine, carbazole, triph boxylic-carbonic anhydride. Further details regarding the enylene, , arsabenzene, Stibabenzene, 2,4,6-triph preparation of azlactones may be found in “Polyazlactones', enylphosphabenzene, m-selenophene, dibenzostannepine, Encyclopedia of Polymer Science and Engineering, Vol. 11, m-tellurophene, phenothiazine, selenanthrene, phenox 2" Ed., John Wiley and Sons, pp. 558-571 (1988). With aphosphine, phenarsazine, phenatellurazine, m-methylcy respect to the above reaction scheme, it will be apparent that clopentadienyl, m-pentamethylcyclopentadienyl, and 1-phe diacyl halide starting materials may be used to produce nylborabenzene. Other suitable aromatic compounds can be dimeric or bis-azlactone initiators, some examples of which found by consulting any of many chemical handbooks. 10 are shown below. These bis-azlactone initiators have the gen Preferred ligands include unsubstituted and substituted eral structure: and bipyridines, tertiary amines, including poly dentate amines such as tetramethyl ethylenediamine and hex amethyl tris-aminoethylamine, acetonitrile, phosphites Such RI RI as (CHO)P, 1,10-phenanthroline, porphyrin, cryptands and 15 R4 R. 7 R. crown ethers, such as 18-crown-6. The most preferred ligands N Q R Q N R are polydentate amines, bipyridine and phosphites. Useful Y n X X 21 ligands and ligand-metal complexes useful in the initiator systems of the present invention are described in Matyjasze (CH2). O st wski and Xia, Chem. Rev., vol. 101, pp. 2921-2990, 2001. O O Examples of olefinically unsaturated monomers that may be polymerized include (meth)acrylates such as ethyl(meth) acrylate, propyl(meth)acrylate, butyl(meth)acrylate, isooctyl (meth)acrylate and other alkyl(meth)acrylates; also function wherein alized (meth)acrylates including glycidyl(meth)acrylate, 25 X is Cl, Br, or a pseudohalogen group, trimethoxysilyl propyl(meth)acrylate, allyl(meth)acrylate, R" is selected from X, H, an alkyl group of 1 to 18 carbon hydroxyethyl(meth)acrylate, hydroxypropyl(meth)acrylate, atoms, a cycloalkyl group having 3 to 14 carbon atoms, an dialkylaminoalkyl(meth)acrylates; fluoroalkyl(meth)acry aryl group having 6 to 12 ring atoms, an arenyl group lates; (meth)acrylic acid, fumaric acid (and esters), itaconic having 6 to 26 carbon atoms, a heterocyclic group having acid (and esters), maleic anhydride; styrene, C.-methyl Sty 30 one ring or two fused rings having 5 to 12 ring atoms and 1 rene; vinyl halides such as vinyl chloride and vinyl fluoride; acrylonitrile, methacrylonitrile; vinylidene halides; buta to 3 heteroatoms selected from S, N, and nonperoxidic O: ; unsaturated alkylsulphonic acids or derivatives R and R are each independently selected from an alkyl thereof, 2-vinyl-4,4-dimethylazlactone, and (meth)acryla group having 1 to 18 carbon atoms, a cycloalkyl group mide or derivatives thereof. Mixtures of such monomers may having 3 to 14 carbon atoms, an aryl group having 5 to 12 be used. 35 ring atoms, an arenyl group having 6 to 26 carbon atoms and 0 to 3 S, N, and nonperoxidic Oheteroatoms, or Rand Initiators of Formula I may be prepared using the general R' taken together with the carbon to which they are ized sequence as shown: attached form a carbocyclic ring containing 4 to 12 ring atoms; O 40 R’ is a divalent alkylene group of 1 to 18 carbon atoms, a cycloalkylene group having 3 to 14 carbon atoms, an aryl X -- HN (CH)-COH group having 6 to 12 ring atoms, oran arenyl group having 6 to 26 carbon atoms, RI R2 R3 R4 Q is a linking group selected from a covalent bond, 45 (—CH2—), CO-O-(CH2) , CO. O. (CH2CH2O). , —CO NR (CH) , —CO-S (CH2). , where o is 1 to 12, and R is H, an alkyl group, a cycloalkyl group, an arenyl group, a heterocyclic group or an aryl group; and n is 0 or 1. O R3 R4 50 Useful azlactone initiators include the following com pounds: x O1us YN1 X NCH-1 CO2H --

R3 4 55 X XYYN R R1 R2 st 60 O Ph O X N In the above Scheme, an amino acid is first acylated, gen > < erally by dissolving the amino acid in aqueous base, followed R O O by treatment with the acyl halide compound under interfacial 65 R = Ph, Me reaction conditions. Cyclization may be effected by treatment x = Cl, Br with acetic anhydride and pyridine, by treatment with carbo US 7,557,177 B2 9 10 catalysts to achieve an effective rate. Acid catalysts such as -continued trifluoroacetic, ethanesulfonic, and toluenesulfonic acids are effective with hydroxyl groups and secondary amines. N f 5 R3 X N R4 Ji-SO N R XYYR2 () (CH2) W S 10 T N O O O O N RI O R3

O cha-l-z- R5 15 X----N: R2 R4 N Bir Br N N R / With respect to the compound R(ZH), m is at least one, O O O O and but preferably m is at least two. The multiple -ZH groups of 2O the polyfunctional compound may be the same or different. N R. Br Multifunctional compounds may be reacted with the azlac N tone compound of Formula I to produce polyfunctional ini O O 2 tiators of Formula II, where m is at least two. Such polyfunc tional initiators allow the preparation of graft, and star (co) Br R O 25 polymers and other useful topologies. O Useful alcohols of the formula R(ZH), include aliphatic and aromatic monoalcohols and polyols. Useful monoalco hols include methanol, ethanol, octanol, decanol, and phenol. It will be understood that the above-depicted compounds The polyols useful in the present invention include aliphatic may be modified as described in Formula I. For example, the so or aromatic polyols having 1 to 30 carbon atoms, at least two bromine atom may be substituted for a chlorine, fluorine or hydroxyl groups. Example of useful polyols include ethylene pseudohalogen group. glycol, propylene glycol, butanediol. 1,3-pentane diol. 2.2- Ring-opened azlactone compounds of Formula II may be oxydiethanol hexanediol poly(pentyleneadipate glycol), poly made by nucleophilic addition of a compound of the formula (tetramethylene ether glycol), poly(ethylene glycol), poly R(ZH), to the azlactone carbonyl of Formula I as shown 35 (caprolactone diol), poly(1.2-butylene oxide glycol), below. In the Scheme below, R is an inorganic or organic trimethylyol ethane, trimethylol propane, trimethyol ami group having one or a plurality of nucleophilic -ZH groups, nomethane, ethylene glycol, 2-butene-1,4-diol, pentaerythri which are capable of reacting with the azlactone moiety of tol, dipentaerythritol, and tripentaerythritol. The term Formula I. R(ZH), may be water. "polyol also includes derivatives of the above-described If organic, R may be a polymeric or non-polymeric 40 polyols such as the reaction product of the polyol with di- or organic group that has a valence of m and is the residue of a poly-isocyanate, or di- or poly-carboxylic acid, the molar nucleophilic group-substituted compound, R(ZH), in ratio of polyol to NCO, or—COOH being 1 to 1. which Z is —O , —S , or NR wherein R' can be a H, Useful amines of the formula R(ZH), include aliphatic an alkyl, a cycloalkyl or aryl, a heterocyclic group, an arenyl and aromatic monoamines and polyamines. Any primary or and m is at least one, preferably at least 2, The organic moiety 45 secondary amine may be employed, although primary amines R has a molecular weight up to 20,000, preferably selected are preferred to secondary amines. Useful monoamines from mono- and polyvalent hydrocarbyl (i.e., aliphatic and include, for example, methyl-ethyl-, propyl-, hexyl-, octyl, aryl compounds having 1 to 30 carbon atoms and optionally dodecyl-, dimethyl-, methyl ethyl-, and aniline. The term Zero to four catenary heteroatoms of oxygen, nitrogen or “di-, or polyamine.” refers to organic compounds containing Sulfur), polyolefin, polyoxyalkylene, polyester, polyolefin, so at least two non-tertiary amine groups. Aliphatic, aromatic, polyacrylate, or polysiloxane backbones. If inorganic, R cycloaliphatic, and oligomeric di- and polyamines all are may comprise silica, alumina or glass having one or a plural considered useful in the practice of the invention. Represen ity of-ZH groups on the Surface. tative of the classes of useful di- or polyamines are 4,4'- In one embodiment, R comprises a non-polymeric ali methylene dianiline, 3.9-bis(3-aminopropyl)-2,4,8,10-tet phatic, cycloaliphatic, aromatic or alkyl-substituted aromatic 55 raoxaspiro5.5undecane, and polyoxyethylenediamine. moiety having from 1 to 30 carbonatoms. In another embodi Many di- and polyamines, such as those just named, are ment, R comprises a polyoxyalkylene, polyester, polyolefin, available commercially, for example, those available from polyacrylate, or polysiloxane polymer having pendent or ter Huntsman Chemical, Houston,Tex. The most preferred di- or minal reactive -ZH groups. Useful polymers include, for polyamines include aliphatic diamines or aliphatic di- or example, hydroxyl, thiol or amino terminated polyethylenes 60 polyamines and more specifically compounds with two pri or polypropylenes, hydroxyl, thiol or amino terminated poly mary amino groups, such as ethylene diamine, hexamethyl (alkylene oxides) and polyacylates having pendant reactive ene diamine, dodecanediamine, and the like. functional groups, such as hydroxyethyl acrylate polymers Useful thiols of the formula R(ZH), includealiphatic and and copolymers. aromatic monothiols and polythiols Useful alkyl thiols Depending on the nature of the functional group(s) of 65 include methyl, ethyl and butyl thiol, as well as 2-mercapto R(ZH), a catalyst may be added to effect the condensation ethanol, 3-mercapto-1,2-propanediol, 4-mercaptobutanol, reaction. Normally, primary amine groups do not require mercaptoundecanol, 2-mercaptoethylamine, 2,3-dimercap US 7,557,177 B2 11 12 topropanol, 3-mercaptopropyltrimethoxysilane, 2-chloroet In the present polymerization, the amounts and relative hanethiol, 2-amino-3-mercaptopropionic acid, dodecyl mer proportions of initiator, transition metal compound and captan, thiophenol, 2-mercaptoethyl ether, and ligand are those effective to conduct atom transfer radical pentaerythritol tetrathioglycolate. Useful soluble, high polymerization (ATRP). Initiator efficiencies with the present molecular weight thiols include polyethylene glycol di(2- initiator System (initiator/transition metal compound/ligand mercaptoacetate), LP-3TM resins supplied by Morton Thiokol system) are generally very good (at least 50%, preferably greater than 80%, more preferably greater than 90%). Inc. (Trenton, N.J.), and Permapol P3TM resins supplied by Accordingly, the amount of initiator can be selected Such that Products Research & Chemical Corp. (Glendale, Calif.) and the initiator concentration is from 10 M to 1M, preferably compounds such as the adduct of 2-mercaptoethylamine and 10 to 10 M. Alternatively, the initiator can be present in a caprolactam. 10 molar ratio of from 10:1 to 10:1, preferably from 10:1 The invention provides multifunctional initiators of For to 5x10:1, relative to monomer. The initiator system will mula II, whereby an azlactone initiator of Formula I is ring generate, during polymerization, the redox conjugate of the opened by a multireactive or multifunctional compound of transition metal compound in an amount Sufficient to revers the formula R(ZH), where m is at least 2, Such multifunc ibly deactivate some portion of radicals formed in a reaction tional initiators may be used to produce branched, star and 15 between said initiator, said transition metal compound and a graft (co)polymers and other topologies. It will also be appar radically polymerizable monomer. ent that such (co)polymers may also be prepared by first The molar proportion of transition metal compound rela polymerizing a monomer using the initiator of Formula I, to tive to initiator is generally that which is effective to polymer produce polymers having an azlactone group at one terminal ize the selected monomer(s), but may be from 0.001:1 to 10:1, end, and then Subsequently reacting the polymers with a preferably from 0.1:1 to 5:1, more preferably from 0.3:1 to polyfunctional compound of the formula R(ZH), where m 2:1, and most preferably from 0.9:1 to 1.1:1. Conducting the is at least 2. polymerization in a homogeneous system may permit reduc ing the concentration of transition metal and ligand Such that In another embodiment, the multifunctional initiators may the molar proportion of transition metal compound to initiator comprise a solid Support having a plurality of initiator moi is as low as 0.0001:1. eties on the surface thereof. Such initiator-functionalized sup 25 Similarly, the molar proportion of ligand relative to transi ports have the general structure (corresponding to Formula tion metal compound is generally that which is effective to II): polymerize the selected monomer(s), but can depend upon the number of coordination sites on the transition metal com pound that the selected ligand will occupy. The amount of IV 30 ligand may be selected Such that the ratio of coordination sites RI O R3 O on the transition metal compound to coordination sites which the ligand will occupy is from 0.1:1 to 100:1, preferably from x-Ho-I-N cis-Il-7-s 0.2:1 to 10:1, more preferably from 0.5:1 to 3:1, and most R2 preferably from 0.5:1 to 2:1. It is possible for a solvent or for 35 a monomer to act as a ligand. The present polymerization may be conducted in bulk, or wherein in a solvent. Solvents, preferably organic, can be used to assist X, R', R. R. R. Z. n and mare as previously described for in the dissolution of the initiator and initiator system in the Formula II and SS is a solid support corresponding to R. polymerizable monomers, and as a processing aid. Prefer The Solid Support material includes functional groups to 40 ably, Such solvents are not reactive with the azlactone group. which initiator molecules of Formula I can be covalently It may be advantageous to prepare a concentrated Solution of the transition metal complex in a small amount of solvent to attached for building large or Small organic compounds. simplify the preparation of the polymerizable composition. Useful functional groups include hydroxyl, amino and Suitable solvents include ethers such as diethyl ether, ethyl thiol functional groups corresponding to -ZH. propyl ether, dipropyl ether, methyl t-butyl ether, di-t-butyl The Support material can be organic or inorganic. It can be 45 ether, glyme(dimethoxyethane), diglyme, diethylene glycol in the form of solids, gels, glasses, etc. It can be in the form of dimethyl ether; cyclic ethers such as tetrahydrofuran and a plurality of particles (e.g., beads, pellets, or microspheres), dioxane; alkanes; cycloalkanes; aromatic hydrocarbon Sol fibers, a membrane (e.g., sheet or film), a disc, a ring, a tube, vents such as benzene, toluene, o-Xylene, m-Xylene, p-Xy or a rod, for example. Preferably, it is in the form of a plurality lene; halogenated hydrocarbon solvents; acetonitrile; lac of particles or a membrane. It can be swellable or non 50 tones such as butyrolactone, and Valerolactones; ketones Such Swellable and porous or nonporous. as acetone, methyl ethyl ketone, methyl isobutyl ketone, The Support material can be a polymeric material that can cyclopentanone, and cyclohexanone; Sulfones Such as tetram be used in conventional Solid phase synthesis. It is chosen ethylene sulfone, 3-methylsulfolane, 2,4-dimethylsulfolane, such that it is generally insoluble in the solvents or other butadiene sulfone, methylsulfone, ethylsulfone, propyl sul components used in Synthetic reactions that occur during the 55 fone, butyl sulfone, methyl vinyl sulfone, 2-(methylsulfonyl) course of Solid phase synthesis. ethanol, and 2,2'-sulfonyldiethanol; Sulfoxides Such as dim ethyl Sulfoxide; cyclic carbonates such as propylene carbon Examples of useable pre-existing Support materials are ate, ethylene carbonate and vinylene carbonate; carboxylic described in G. B. Fields et al., Int. J. Peptide Protein Res., 35, acid esters such as ethyl acetate, Methyl CellosolveTM and 161 (1990) and G. B. Fields et al., in Synthetic Peptides: A methyl formate; and other solvents such as methylene chlo User's Guide, G. A. Grant, Ed., pages 77-183, W. H. Freeman 60 ride, nitromethane, acetonitrile, glycol sulfite and 1.2- and Co., NewYork, N.Y. (1992). The support material is in the dimethoxyethane(glyme), mixtures of Such solvents, and form of an organic polymeric material. Such as polystyrenes, Supercritical solvents (such as CO2). The present polymeriza polyalkylenes, nylons, polysulfones, polyacrylates, polycar tion may also be conducted in accordance with known Sus bonates, polyesters, polyimides, polyurethanes, etc. and hav pension, emulsion and precipitation polymerization pro ing hydroxyl, amino or thiol Substituents on the Surface. For 65 CCSSCS. pre-existing Support materials, a preferred Support material is The polymerization reaction may be controlled by match polystyrene. ing the reactivity of the groups in the initiator with the mono US 7,557,177 B2 13 14 mer, and by matching the energetics of bond breaking and Such (co)polymers have the general formula Az-(M'), bond forming in dormant species, e.g., dormant polymer (M'),(M), ... (M)-X, whereinX is Cl, Br or a pseudohalo chains and transition metal species. Matching the reactivities gen group. M' to Mare each polymerized monomer units of the initiator with the monomer depends to Some degree on derived from a radically (co)polymerizable monomer unit the radical stabilizing effects of the substituents. Thus, where having an average degree of polymerization X, each X is the monomer is a halogenated alkene, one may select an independent, and AZ is an azlactone group or a ring-opened initiator where of R' and/or R are lower alkyl groups. On the azlactone group of Formula III. Further, the polymer product other hand, if one wishes to polymerize an arene- or ester retains the functional group “X” at one terminal end of the stabilized monomer (e.g., a (meth)acrylate, acrylonitrile or polymer necessary to initiate a further polymerization (or styrene), one may select an initiator which is stabilized by a functionalization). The polymer product further comprises similar group, wherein one of R' and/or R is aryl, or arenyl. 10 either the azlactone moiety or the ring-opened azlactone moi Such matching of Substituents on the initiator and monomer ety of the initiator at the other terminal end, which may be provides a beneficial balance of the relative reactivities of the further reacted or functionalized as desired. Because the two initiator and monomer. terminal moieties have different functionality and reactivity, Preferably, the monomer, initiator, transition metal com each terminus may be independently functionalized. pound and ligandare selected Such that the rate of initiation is 15 The terminal “X” group may be functionalized indepen not less than 1,000 times (preferably not less than 100 times) dently from the terminal'Az’ group. For example, where X is slower than the rate of propagation and/or transfer of the X Br, the terminal bromine may be reduced to a hydrogen by group to the polymer radical. In the present application, treatment with BusSnH, may be converted to an acyl group by “propagation” refers to the reaction of a polymer radical with treatment with a trimethylsilyl vinyl ether, and may be con a monomer to form a polymer-monomer adduct radicals. verted to an azide by treatment with NaNs, which in turn may Polymerizing may be conducted at a temperature of from be converted to an amine by reduction with LiAlH. Other –78 to 200° C., preferably from 0 to 160° C. and most pref. methods of converting a terminal halide group to other func erably from 20 to 140°C. The reaction should be conducted tional groups are known in the art, and reference may be made for a length of time sufficient to convert at least 10% (prefer to Chem. Rev., vol. 101, pp. 2921-2990, 2001. ably at least 50%, more preferably at least 75% and most The present invention encompasses a novel process for preferably at least 90%) of the monomer to polymer. Typi 25 preparing random, block, multi-block, star, gradient, random cally, the reaction time will be from several minutes to 5 days, hyperbranched and dendritic copolymers, as well as graft or preferably from 30 minutes to 3 days, and most preferably “comb' copolymers. Each of these different types of copoly from 1 to 24 hours. mers will be described hereunder. Polymerizing may be conducted at a pressure of from 0.1 to Since ATRP is a “living or “controlled polymerization, it 100 atmospheres, preferably from 1 to 50 atmospheres and 30 can be initiated and terminated as desired. Thus, in one most preferably at ambient pressure (although the pressure embodiment, once the first monomer is consumed in the may not be measurable directly if conducted in a sealed initial polymerizing step, a second monomer can then be vessel). An inert gas such as nitrogen or argon may be used. added to form a second block on the growing polymer chain If desired, the polymerization process may further com in a second polymerizing step. Additional polymerizations prise the steps of isolating the resulting polymer from the 35 with the same or different monomer(s) can be performed to Solvent, monomer, and initiators system, and may further prepare multi-block copolymers. The Subsequent polymer comprise the step of recovering and recycling the initiator and steps may use the same initiator System as in the first step of transition metal complex of the initiator system. The transi the polymerization, or another may be chosen to reflect or tion metal may be isolated by many techniques known in the “match' the different reactivity of the subsequent monomers. art including addition of a solvent in which the transition 40 Because ATRP is radical polymerization, blocks can be metal complex is insoluble, addition of a ligand that reduces prepared in essentially any order. One is not necessarily lim the solubility of the transition metal complex in a chosen ited to preparing block copolymers where the sequential solvent, filtration with silica, alumina or Celite, and centrifu polymerizing steps must flow from the least stabilized poly gation. In many instances, it is preferred to further function merintermediate to the most stabilized polymer intermediate, alize the azlactone terminal group prior to separation of the Such as is necessary in ionic polymerization. Thus, one can transition metal complex as many separation techniques, such 45 prepare a multi-block copolymer in which a polyacrylonitrile as contact with silica, can result in ring-opening of the azlac or a poly(meth)acrylate block is prepared first, then a styrene tone group. Thus it is preferred to first react the product or butadiene block is attached thereto, etc. (co)polymer with a compound of the formula R(ZH), to Furthermore, a linking group is not necessary to join the functionalize the terminal azlactone group prior to isolation different blocks of the present block copolymer. One can of the transition metal complex, as previously described. 50 simply add Successive monomers to form Successive blocks. The (co)polymers obtained by the method of the invention Further, it is also possible (and in Some cases advantageous) may be described as telechelic (co)polymers comprising to first isolate a (co)polymer produced by the present ATRP polymerized units of one or more free radically (co)polymer process, then react the polymer with an additional monomer izable monomers (as previously described), a first azlactone using a different initiator/catalyst system (to “match' the terminal group derived from the initiator of Formula I and a 55 reactivity of the growing polymer chain with the new mono second terminal group selected from the group derived from mer). In such a case, the product polymer having a terminal X. Alternatively, when using the initiators of Formula II, the “X” group acts as the new initiator for the further polymer first terminal group “AZ” will comprise the ring-opened resi ization of the additional monomer. Since the novel initiators due of the azlactone group of the Formula III: provide a reactive group “AZ” at a terminal end of the poly mer, linking groups may be used to join two polymer blocks. III 60 For example, in one embodiment, a polymer prepared in R1 O R3 O accord with the present invention, and having an azlactone (CH2) --z R5 group at one terminus, may be reacted with a second polymer ----N: block having a nucleophilic terminal group. R2 Statistical copolymers may be produced using the initiators 65 of the present invention. Such copolymers may use 2 or more where R', R. R. R. R. Z, Q and n are as previously monomers in a range of about 0-100% by weight of each of defined. the monomers used. The product copolymer will be a func US 7,557,177 B2 15 16 tion of the molar amounts of the monomers used and the relative reactivity of the monomers. -continued The present invention also provides graft or “comb” copolymers. Here, a first (co)polymer having pendent nucleo R1 philic functional groups, such hydroxy-, amino- or thio HO groups, etc. is provided. An example of a useful (co)polymers N R2 include hydroxyethyl acrylate (co)polymers. Next, the reac tive functional groups of the first (co)polymer is reacted with the azlactone initiators of Formula I to provide a (co)polymer having pendent, ring-opened initiator moieties, the reaction product having the structure of Formula II, where R is the 10 To a stirring mixture of 2-aminoisobutyric acid (52.08 g. residue of the first (co)polymer. This product (co)polymer 0.51 mol), sodium hydroxide (20.20 g, 0.51 mol), 200 mL may then be used as an initiator to polymerize the previously water, and 50 mL chloroform cooled to -12°C., was added a described monomers to produce a comb (co)polymer. Alter solution of 2-bromopropionyl bromide (100 g, 0.46 mol) in natively, the first (co)polymer may be reacted with a telech 150 mL chloroform over 15 minutes. The temperature was elic (co)polymer of the invention, whereby the reactive 'Az' 15 maintained between -15 and -12°C. during the addition. The terminal group reacts with the pendent reactive group of the first (co)polymer. reaction mixture was then allowed to warm to room tempera Gradient or tapered copolymers can be produced using ture and the precipitated solid was filtered. The solid was ATRP by controlling the proportion of two or more mono mixed with 700 mL hot toluene, and then cooled. The white mers being added. For example, one can prepare a first block solid was then filtered and dried under vacuum. A yield of or an oligomer of a first monomer, then a mixture of the first 77.60 g (70%) was obtained. monomer and a second distinct monomer can be added in proportions of from, for example, 1:1 to 9:1 of first monomer Example 2 to second monomer. After conversion of all monomer(s) is complete, sequential additions of first monomer-second 25 Preparation of monomers mixtures can provide Subsequent “blocks' in 2-(1-bromoethyl)-4,4-dimethyl-4H-oxazol-5-one which the proportions of first monomer to second monomer vary. Thus, the invention provides copolymers obtained from O two or more radically (co)polymerizable monomers wherein RI HO He the copolymer has a composition that varies along the length NH R2 of the polymer chain from azlactone terminus to opposite 30 terminus based on the relative reactivity ratios of the mono mers and instantaneous concentrations of the monomers dur ing polymerization

EXAMPLES 35 All reagents unless otherwise noted were purchased from Aldrich (Milwaukee, Wis.) and were used in their delivered condition. Polymerizable reagents were stripped of inhibitors prior to use by passing them through an alumina column (also 40 supplied by Aldrich). Solvents were purchased from EM Sci To a stirring mixture of 2-(2-bromopropionylamino)-2- ence located in Gibbstown, N.J. methyl propionic acid (50.00 g, 0.21 mol), triethylamine Glossary (23.37g, 0.23 mol), and 150 mL acetone cooled to 5°C., was “bpy’ means bipyridyl: added dropwise a solution of ethyl chloroformate (25.07 g. “MMA” means methyl methacrylate: 45 0.23 mol) in 40 mL acetone. After full addition, the mixture “PMMA' means poly(methyl methacrylate); was allowed to warm to room temperature, and was stirred for “P” means polydispersity index; two hours. The mixture was filtered, and the solid was washed “bromo-di-methyl azlactone' means 2-(1-bromo-1-methyl with ether. The solvent was then removed under vacuum, and ethyl)-4,4-dimethyl-4H-oxazol-5-one: the residue was filtered. The filtrate was distilled under “DBU’ means 1,8-diazabicyclo5.4.0]undec-7-ene; and 50 reduced pressure to give a colorless oil (bp 63-64° C. at 1 “GPC' means gel permeation chromatography. mmHg). A yield of 34.73 g (75%) was obtained. Example 1 Example 3 Preparation of 55 Preparation of 2-(2-chloro acetylamino)-2-methyl 2-(2-bromopropionylamino)-2-methylpropionic acid propionic acid O O R1 60

OH OH HN HN 65 US 7,557,177 B2 17

-continued -continued

R1 OH HO N R2 HN O O R1 HO N R2 10 H To a stirring mixture of 2-aminoisobutyric acid (165.8 g. O X 1.61 mol), sodium hydroxide (64.4g, 1.61 mol), and 800 mL X = Br, R =CHR = CH water cooled to 5°C., was added two separate solutions of chloroacetyl chloride (200 g, 1.77 mol) and sodium hydrox A stirring mixture of 2-aminoisobutyric acid (28.5g, 0.28 ide (70.8 g. 1.77 mol) in 143 mL water. The temperature was 15 maintained between 5 to 10° C. during the addition. The mol), sodium hydroxide (11.1 g, 0.28 mol), 115 mL of water, reaction mixture was then allowed to warm to room tempera and 30 mL of chloroform was cooled to -10° C. and stirred ture and the solution was acidified with 165 mL of concen vigorously while a solution of 2-bromisobutyryl bromide trated aq. HC1. The precipitated solid was filtered and dried (57.0 g, 0.25 mol) in 85 mL of chloroform was added drop under vacuum. A yield of 180.4 g (62%) was obtained. wise. When addition was complete, the reaction flask was removed from the cold bath and allowed to warm to room Example 4 temperature. The mixture stirred for 15 hours. Concentrated HCl (10 mL) was then added to the mixture and stirring was Preparation of continued for another 30 minutes. A white solid (32.0 g) was 2-(chloromethyl)-4,4-dimethyl-4H-oxazol-5-one 25 filtered off, and the aqueous and organic phases of the filtrate were separated. The organic phase was dried over magnesium Sulfate, filtered, and evaporated at reduce pressure to leave a white solid (21.0 g). The two solid portions were combined 30 and recrystallized from toluene to afford 27.1 g (43%) of the HO title compound as a white solid with IR and NMR spectra NH consistent with the desired product. Example 6 35 Preparation of 2-(1-bromo-1-methyl ethyl)-4,4-dim ethyl-4H-oxazol-5-one

40

To stirring mixture of 2-(2-chloro acetylamino)-2-methyl HO propionic acid (18.04 g., 0.10 mol), triethylamine (11.13 g, NH 0.11 mol), and 100 mL of acetone cooled with an ice bath was 45 added ethyl chloroformate (10.52 mL, 0.11 mol) over 10 minutes. The reaction mixture was warmed to room tempera ture and stirred for 2 hours. The mixture was then filtered, and the filtrate was concentrated under vacuum. Hexane (200 mL) was added to the residue and the mixture was filtered. After 50 removal of the solvent under vacuum, the residue was dis tilled under reduced pressure (bp 59-60° C. at 7 mmHg) to give a colorless oil. A yield of 13.18 g (82%) was obtained. A solution of ethyl chloroformate (32.4g, 0.30 mol) in 50 Example 5 55 mL acetone was added dropwise to a stirring mixture of 2-(2-bromo-2-methyl propionylamino)-2-methylpropionic Preparation of 2-(2-bromo-2-methyl acid (67.9 g, 0.27 mol) and triethylamine (30.0g, 0.30 mol) in propionylamino)-2-methyl-propionic acid 200 mL of acetone at -15° C. When addition was complete, 60 the mixture was stirred at room temperature for 2 hours, and the white solid was filtered off and washed with 100 mL of ether. The combined filtrates were reduced in volume to about 200 mL at reduced pressure and cooled in a refrigerator at about 5°C. overnight. The small amount of white solid that 65 had separated was removed by filtration, and the solvents were evaporated at reduced pressure. The residue was taken up in 300 mL of ether, filtered, and the solvent evaporated to US 7,557,177 B2 19 20 leave the title compound (61.5 g., 98%) with IR and NMR spectra consistent with the desired product. TABLE 8.1 Example 7 GPC data for ATRP of MMA using brono dimethyl azlactone. Time (min.) M (10) M (10) P Preparation of 2-(2-bromo-2-methyl propiony 10 1.87 1.73 1.08 lamino)-2-methyl propionic acid 2.2-bis-2-(2- 2O 2.86 2.45 1.17 bromo-2-methyl propionylamino)-2-methyl propio 30 2.97 2.38 1.25 40 3.29 2.57 1.28 nyloxymethyl-butyl ester 10 50 3.51 2.71 1.29 60 3.95 3.05 1.29 70 S.10 3.90 1.31

R1 R2 The data in Table 1 demonstrates that the molecular weight 15 increases steadily overtime and that the polydispersity is <1.1 f -X. X -- at lower conversions and increases to 1.3 at higher conver N sions. These characteristics are indicative of a living/con trolled polymerization process. HO Example 9 Use of a Multi-Functional Initiator to Synthesize HO OH poly(methyl methacrylate) PMMA Star Polymers

O 25 R1 A 100 mL three-necked reaction vessel, equipped with O manual stirring, N2 inlets and outlets, and a thermocouple, N R2 and was charged with MMA, 21.025 g, 210 mmol), the ini H tiator of Example 7 (1.115 g, 4 mmol), toluene (46g, 33 wt. O X 3 % solids) and bpy (1.88 g. 12 mmol). The solution were 30 stirred and purged with N for a period of 30 minutes, then heated to 50° C. via an oil bath powered by a J-Kem digital temperature controller. CuCl (0.392 g, 4 mmol), stored and A mixture of 2-(1-bromo-1-methyl ethyl)-4,4-dimethyl weighed in an inert atmosphere, was added Such that the molar ratios of the reagents used were monomerinitiator: 4H-oxazol-5-one (17.3 g, 74 mmol), trimethylolpropane 35 (3.30 g, 24.6 mmol), and (0.10 g, 0.9 CuCl:ligand=105:2:2:6. The theoretical M., of the final poly mer at 100% conversion using this ratio was about 16,000 mmol) was heated in a sealed vessel at 75° C. for 17 hours. g/mol or about 5.300 g/mol per arm. The reaction was allowed The resulting product, a white solid, was recrystallized twice to proceed for 6 hours. from aqueous ethanol to afford the title compound (12.7 g. The M as determined by GPC, of the resulting poly 62%) as a white solid with IR and NMR spectra consistent 40 (MMA) star polymer was 16,400, which compared favorably with the desired product. to the theoretical value. Furthermore, the star polymer had a polydispersity, P. of 1.24. Example 8 Example 10 Controlled Polymerization of methyl methacrylate 45 Using a Functional Initiator to Yield Star Polymers In a 50 mL three-necked reaction vessel equipped with Through Chemical Modification manual stirring, N2 inlets and outlets, and a thermocouple, MMA (21.025 g, 210 mmol), bromo-di-methyl azlactone 50 Linear PMMA arms were synthesized according to the (0.94 g, 4 mmol), and bpy (1.88 g. 12 mmol) were stirred and methods taught in Example 8 and GPC was used to confirm purged with N for a period of 30 minutes. The solution was the M of the polymer to be 10,300 g/mol (P=1.18). In a also heated to 70° C. via an oil bath powered by a J-Kem 9-dram glass vial, tris-aminoethylamine (0.0142g, 9.7x10 digital temperature controller. CuC1 (0.392 g., 4 mmol), mol) was added to a 33 wt.% toluene solution containing 3.00 stored and weighed in an inert atmosphere, was added Such 55 g. (2.91x10" mol) of functional PMMA arms. The vial was that the molar ratios of the reagents used were monomer: capped and placed in a heated shaker bath at 60° C. for 16 initiator:CuCl:ligand=105:2:2:6. The theoretical M of the hours. The resulting star polymer had a M., of 34,900 g/mol final polymer at 100% conversion using this ratio was about and P=1.10 as determined by GPC. 5,300 g/mol. The reaction was allowed to proceed for 70 minutes. 60 Example 11 A Syringe was used to take aliquots of the mixture through Using a Functional Initiator to Yield Star Polymers a rubber septa as time passed. The aliquots were immediately Through Chemical Modification. quenched in a large excess of methanol. The precipitate was then filtered, dried and submitted for GPC. 65 Linear PMMA arms were synthesized according to the The results of the polymerization of MMA are shown in methods taught in Example 8 and GPC was used to confirm Table 8.1 and are plotted in FIG.8.1. the M, of the polymer to be 10,300 g/mol (P=1.18). US 7,557,177 B2 21 22 In a 9-dram glass vial, tris-aminoethyl amine (0.0142 g, with R=0.9998, Beyond this point, the reaction is >95% 9.7x10 mol) was added to a 33 wt.% toluene solution complete. This indicates that the polymerization is first order containing functional PMMA (3.00g, 2.91x10" mol) arms. in monomer. A catalytic amount of DBU was added to aid in reaction We claim: completion. The vial was capped and placed in a heated 5 1. A telechelic (co)polymer of the structure: shaker bath at 60° C. for 16 hours. The resulting star polymer AZ-(M)-X, wherein had a M., of 30,500 g/mol and P=1.11 as determined by GPC. X is Cl, Br or a pseudohalogen group; Example 12 M' is a monomer unit derived from a radically (co)poly 10 merizable monomer unit having an average degree of Using a Functional Initiator to Synthesize Block polymerization X, and Copolymers AZ is a ring-opened azlactone group of the formula: A three-armed PMMA macro-initiator was synthesized according to the methods taught in Example 9. The macro 15 RI O O initiator possessed a Mw of 37,000 g/mol and a M., of 18,800 g/mol. In a 100 mL three-necked reaction vessel equipped (CH2) --z with manual stirring, N inlets and outlets, and a thermo ---|-Nil couple, three-armed PMMA macro-initiator (9.69 g, 0.515 R2 mmol), n-butyl acrylate (10.92 g, 0.085 mol), toluene (40 g, 33 wt.% solids) and bpy (0.724g, 4.6 mmol) were stirred and wherein RandR are eachindependently selected from X, purged with N for a period of 30 minutes. The solution was H, an alkyl group, a cycloalkyl group, a heterocyclic heated to 70° C. by an oil bath powered by a J-Kem digital group, an arenyl group and an aryl group, or R' and R' temperature controller. CuC1 (0.1529 g, 1.5 mmol), stored taken together with the carbon to which they are attached and weighed in an inert atmosphere, was added Such that the 25 form a carbocyclic ring; molar ratios of the reagents used were monomerinitiator: CuCl:ligand=120:1:3:9. The reaction was allowed to proceed R and Rare each independently selected from an alkyl for 8 hours. After moderate conversion, the block copolymer group, a cycloalkyl group, an aryl group, an arenyl was determined by GPC to possess a Mw of 50,700 g/mol and group, or R and R taken together with the carbon to a M, of 26.300 g/mol. 30 which they are attached form a carbocyclic ring; R is an organic or inorganic group, Example 13 Q is a linking group selected from a covalent bond, Controlled Polymerization in Real-Time by IR (—CH2—), CO-O-(CH2) , CO. O. Spectroscopy (CHCHO) , CO. NR (CH) , CO 35 S—(CH) , where o is 1 to 12, A ReactIR 1000 (ASIApplied Systems, Millersville, Md.) Z is O, NH, S or NR, wherein R is H, an alkyl group, a infra-red spectrometer, was fitted with a silicon ATR probe to cycloalkyl group, an arenyl group, a heterocyclic group provide IR spectra in real time and in-situ. The data was or an aryl group; and processed to give the kinetic parameters of the system. The 40 n is 0 or 1. procedure is similar to a conventional lab scale polymeriza 2. The telechelic (co)polymer of claim 1 having a molecu tion with the exception of the incorporation of an IR probe lar weight distribution of less than 2.0. into the solution. The IR spectrometer scanned the solution at 3. The telechelic copolymer of claim 1 comprising two or set intervals and stored the spectra to obtain quantitative data more blocks of units obtained from free radically (co)poly related to the appearance and disappearance of various spe 45 cies. Also, the spectra show the azlactone had not been ring merizable monomers, wherein the block copolymer has an opened and remained reactive. In particular, the intensity of aZlactone residue at one terminal end and, at the other termi the carbon-carbon double bond stretching vibration in acry nal end, a member selected from the group consisting of Cl, late-related monomers is directly proportional to the concen Br, and a pseudohalogen. tration of the monomer in Solution. Thus recording the inten 50 4. The telechelic copolymer of claim 3 comprising poly sity vs. time can provide kinetic information on a vinyl merized units obtained from two or more radically (co)poly polymerization. merizable monomers wherein the copolymer has a composi In a 250 mL three-necked reaction vessel equipped with tion that varies along the length of the polymer chain from manual stirring, N inlets and outlets, and a thermocouple, aZlactone terminus to opposite terminus based on the relative and an IR probe, methylmethacrylate (26.4 g), (2-bromo-di 55 reactivity ratios of the monomers and instantaneous concen methyl azlactone (1.153 g), toluene (26.4 g) and bpy (2.1 g) trations of the monomers during polymerization. were stirred and purged with N for a period of 30 minutes. 5. The telechelic (co)polymer of claim 1, wherein said The solution was also heated to 70° C. via an oil bath powered (co)polymer comprises polymerized monomer units selected by a J-Kem digital temperature controller. An initial IR scan from the group consisting of from (meth)acrylic acid and was taken as a start point of the reaction. CuC1 (0.4953 g). 60 esters thereof. fumaric acid and esters thereof; itaconic acid stored and weighed in an inert atmosphere, was added imme and esters thereof maleic anhydride; styrene, C.-methyl Sty diately after the spectrum was completed. rene; vinyl halides; (meth)acrylonitrile; vinylidene halides: The intensity of the vinyl peak at 1640 cm was monitored butadienes; unsaturated alkylsulphonic acids and esters and at intervals of 30 seconds to 5 minutes over a total reaction halides thereof, and (meth)acrylamides; and mixtures time of 8 hours. A plot of InCM/M) vs. time (where Mo is the 65 thereof, said (co)polymer having a ring-opened azlactone initial concentration of monomer and M is the concentration residue at one end of the (co)polymer chain and a radically at time t) for data out to 340 minutes yielded a straight line transferable group at the other end of the (co)polymer chain. US 7,557,177 B2 23 24 6. The telechelic copolymer of claim 1 having the structure Z is O, NH, S or NR, wherein R is H, an alkyl group, a AZ-(M),(M)-(M)x... (M)-X, wherein cycloalkyl group, an arenyl group, a heterocyclic group X is Cl, Br or a pseudohalogen group; or an aryl group; and M' to M are each polymer blocks of monomer units n is 0 or 1. derived from a radically (co)polymerizable monomer 7. The telechelic copolymer of claim3 comprising random, units having an average degree of polymerization X, block, multi-block, star, gradient, random hyperbranched, dendritic, graft and comb copolymers. each X is independent, and 8. The telechelic copolymer of claim 1 wherein Risa solid AZ is a ring-opened azlactone group of the formula: Support. 10 9. The telechelic copolymer of claim 1 wherein said solid RI O R3 O Support is in the form of a plurality of particles or a mem brane. 10. The telechelic copolymer of claim8, wherein said solid ---|-Nil cis-Il-2 R5 Support comprises polystyrenes, polyalkylenes, nylons, R2 R4 15 polysulfones, polyacrylates, polycarbonates, polyesters, polyolefins, polyimides, polyurethanes having hydroxyl, wherein RandR are each independently selected from X, amino or thiol substituents on the surface thereof. H, an alkyl group, a cycloalkyl group, an arenyl group, a 11. The telechelic copolymer of claim 1 wherein R is an heterocyclic group and an aryl group, or R' and R taken aliphatic, cycloaliphatic, aromatic or alkyl-substituted aro together with the carbon to which they are attached form 20 matic moiety having from 1 to 30 carbon atoms. a carbocyclic ring; 12. The initiator of claim 1 wherein R comprises silica, R and R are each independently selected from an alkyl alumina or glass having a plurality of -ZH groups on the group, a cycloalkyl group, an aryl group, an arenyl surface thereof, wherein Z is O, NH, S or NR, wherein R is group, or R and R' taken together with the carbon to H, an alkyl group, a cycloalkyl group, an arenyl group, a which they are attached form a carbocyclic ring; 25 heterocyclic group or an aryl group. R is an organic or inorganic group, 13. The initiator of claim 1, wherein R is derived from a Q is a linking group selected from a covalent bond, polymer having a plurality of nucleophilic ZH groups, where (—CH2—), CO-O-(CH2) , CO. O. Z is O, NH, S or NR, wherein R is H, an alkyl group, a (CH2CH2O), . CO. NR (CH) , CO cycloalkyl group, an arenyl group, a heterocyclic group or an S—(CH) , where o is 1 to 12, and R is H, an alkyl 30 aryl group. group, a cycloalkyl group or an aryl group;

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION

PATENT NO. : 7,557,177 B2 Page 1 of 3 APPLICATIONNO. : 1 1/868793 DATED : July 7, 2009 INVENTOR(S) : Fansler et al.

It is certified that error appears in the above-identified patent and that said Letters Patent is hereby corrected as shown below:

Column 1. Line 43, delete “36-40, and insert -- 36-40. --. Column 4. Line 9, after “thereof insert -- . --. Line 62, delete "atoms. and insert -- atoms. --. Column 6. Line 57, delete “norbomadiene, and insert -- norbornadiene. --. Column 7. Line 16, delete “-crown-6, and insert ---crown-6. --. Line 34, delete “thereof, and insert -- thereof.--. Column 9. Line 37, delete “-ZH and insert ---ZH --. Line 45, delete “least 2, and insert -- least 2. --. Line 53, delete “-ZH and insert -- —ZH --. Line 59, delete “-ZH and insert -- —ZH --. Column 10, Line 19, delete “-ZH and insert -- —ZH --. Column 11. Line 14, delete “least 2, and insert -- least 2. --. Line 44, delete “-ZH. and insert ---ZH. --. Column 12, Line 21, delete “1.1:1, and insert -- 1.1:1. --. Line 34, delete “2:1, and insert -- 2:1. --. Column 15. Line33, after “polymerization insert --. --. Column 17. Line 40, delete “X = Br, R = H, R = CH, and insert -- X = Cl, R = R = H --.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION

PATENT NO. : 7,557,177 B2 Page 2 of 3 APPLICATIONNO. : 1 1/868793 DATED : July 7, 2009 INVENTOR(S) : Fansler et al.

It is certified that error appears in the above-identified patent and that said Letters Patent is hereby corrected as shown below:

Column 18. Line 52, delete “X = Br, R = H, R = CH, and insert -- X = Br, R = CH, R = CH, --. Column 19. Line 13-29, delete

and insert:

R2 ) Os/ X + laus // NH Y N HO O O X

Line 57, delete “:6, and insert -- :6. --.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION

PATENT NO. : 7,557,177 B2 Page 3 of 3 APPLICATIONNO. : 1 1/868793 DATED : July 7, 2009 INVENTOR(S) : Fansler et al.

It is certified that error appears in the above-identified patent and that said Letters Patent is hereby corrected as shown below:

Column 20, Line 35, delete “M,” and insert -- M --. Line 67, delete “M,” and insert -- M --. Column 21, Line 15, delete “9, and insert --9. --. Line 27, delete “:9, and insert -- :9. --. Line 65, delete “In(Mo/M) vs. and insert -- ln(Mo/M)--. Column 22, Line 1, delete “9998, and insert -- 9998. --. Column 24. Line 22, delete “-ZH and insert ---ZH --. Line 27, delete “ZH and insert -- —ZH --.

Signed and Sealed this Seventeenth Day of November, 2009

David J. Kappos Director of the United States Patent and Trademark Office